{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T07:01:40Z","timestamp":1767164500580,"version":"build-2238731810"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:00:00Z","timestamp":1505174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T00:00:00Z","timestamp":1510099200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R35 GM118101"],"award-info":[{"award-number":["R35 GM118101"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AI00758"],"award-info":[{"award-number":["T32 AI00758"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","award":["UM-Israel Partnership for Research"],"award-info":[{"award-number":["UM-Israel Partnership for Research"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","award":["Rackham Graduate School"],"award-info":[{"award-number":["Rackham Graduate School"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2017,11,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    \u2014a Gram-positive, spore-forming bacterium\u2014causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires\n                    <jats:italic>B.\u00a0anthracis<\/jats:italic>\n                    to employ petrobactin, an iron-scavenging small molecule known as a siderophore. Petrobactin biosynthesis is mediated by\n                    <jats:italic>asb<\/jats:italic>\n                    gene products, and import of the iron-bound (holo)-siderophore into the bacterium has been well studied. In contrast, little is known about the mechanism of petrobactin export following its production in\n                    <jats:italic>B.\u00a0anthracis<\/jats:italic>\n                    cells. Using a combination of bioinformatics data, gene deletions, and laser ablation electrospray ionization mass spectrometry (LAESI-MS), we identified a resistance-nodulation-cell division (RND)-type transporter, termed ApeX, as a putative petrobactin exporter. Deletion of\n                    <jats:italic>apeX<\/jats:italic>\n                    abrogated export of intact petrobactin, which accumulated inside the cell. However, growth of \u0394\n                    <jats:italic>apeX<\/jats:italic>\n                    mutants in iron-depleted medium was not affected, and virulence in mice was not attenuated. Instead, petrobactin components were determined to be exported through a different protein, which enables iron transport sufficient for growth, albeit with a slightly lower affinity for iron. This is the first report to identify a functional siderophore exporter in\n                    <jats:italic>B.\u00a0anthracis<\/jats:italic>\n                    and the\n                    <jats:italic>in vivo<\/jats:italic>\n                    functionality of siderophore components. Moreover, this is the first application of LAESI-MS to sample a virulence factor\/metabolite directly from bacterial culture media and cell pellets of a human pathogen.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    <jats:italic>Bacillus anthracis<\/jats:italic>\n                    requires iron for growth and employs the siderophore petrobactin to scavenge this trace metal during infections. While we understand much about petrobactin biosynthesis and ferric petrobactin import, how apo-petrobactin (iron free) is exported remains unknown. This study used a combination of bioinformatics, genetics, and mass spectrometry to identify the petrobactin exporter. After screening 17 mutants with mutations of candidate exporter genes, we identified the\n                    <jats:underline>a<\/jats:underline>\n                    po-\n                    <jats:underline>p<\/jats:underline>\n                    etrobactin\n                    <jats:underline>ex<\/jats:underline>\n                    porter (termed ApeX) as a member of the resistance-nodulation-cell division (RND) family of transporters. In the absence of ApeX, petrobactin accumulates inside the cell while continuing to export petrobactin components that are capable of transporting iron. Thus, the loss of ApeX does not affect the ability of\n                    <jats:italic>B.\u00a0anthracis<\/jats:italic>\n                    to cause disease in mice. This has implications for treatment strategies designed to target and control pathogenicity of\n                    <jats:italic>B.\u00a0anthracis<\/jats:italic>\n                    in humans.\n                  <\/jats:p>","DOI":"10.1128\/mbio.01238-17","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T20:10:50Z","timestamp":1505247050000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Petrobactin Is Exported from\n                    <i>Bacillus anthracis<\/i>\n                    by the RND-Type Exporter ApeX"],"prefix":"10.1128","volume":"8","author":[{"given":"A. 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